The biosynthesis of mammalian morphine from isoquinoline precursor alkaloids takes a different course from that in the opium poppy at the stage of (S)-3'-hydroxy-N-methylcoclaurine. This isoquinoline, on O- methylation with (S)-adenosylmethionine in the presence of mammalian catechol O-methyltransferase afforded almost exclusively (S)-orientaline, and not (S)-reticuline as required for further conversion into morphinan alkaloids and morphine.